Abstract: This invention is directed towards substituted aminoquinuclidine compounds useful as delta-opioid receptor modulators, delta-opioid receptor agonists useful as analgesics and delta-opioid receptor antagonists useful as immunosuppressants, antiinflammatory agents, agents for the treatment of neurological and psychiatric conditions, medicaments for drug and alcohol abuse, agents for treating gastritis and diarrhea, cardiovascular agents and agents for the treatment of respiratory diseases.

Abstract: DNAs encoding the human histamine H3 receptor have been cloned and characterized. The recombinant protein is capable of forming biologically active histamine H3 receptor protein. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified.

Abstract: This invention relates to nucleic acid encoding guinea pig PAR 4 and to the protein encoded thereby. The guinea pig DNA and protein are useful for the development of models of human platelet aggregation. The invention further relates to an animal model to assess the role of PAR antagonists in thrombosis.

Abstract: The present invention relates to novel substituted diamine derivatives for the formula wherein R1, R2, R3, R4, X1, X2, X3, X4, A, Y and n are as described in the specification, pharmaceutical compositions containing them and intermediates used in their manufacture. More particularly, the compounds of the invention are motilin receptor antagonists useful for the treatment of associated conditions and disorders such as gastrointestinal reflux disorders, eating disorders leading to obesity and irritable bowel syndrome.

Abstract: The present invention provides nucleic acid and polypeptide sequences describing a novel isoform of the ?2? subunit of a voltage gated calcium channel, herein named as ?2?-4. The isolated nucleic acid or polypeptide molecule of the invention can be used in diagnosing and treating a disease or disorder associated with a defective ?2?-4 subunit, such as seizure-related syndromes, anxiety, multiple sclerosis, and the like.

Abstract: The present invention is directed to a one-step process for the preparation of fructopyranose sulfamate derivatives of the general formula (I) wherein X, R1, R3, R4, R5 and R6 are as described in the specification.

Abstract: This invention relates to an agent for the protection of retinal neurons which comprises, as an effective ingredient, sulfamate derivative having the following formula: and to a method for the protection of retinal neurons by using said sulfamate derivative.

Abstract: A transgenic animal with alterations in the histamine H3 receptor gene is prepared by introduction of an altered histamine H3 receptor gene into a host animal. The resulting transgenic animals do not produce functional histamine H3 receptor molecules. Cells and cell lines derived from these animals also contain the altered histamine H3 receptor gene.

Abstract: The present invention relates to a process for preparing tetrasubstituted imidazole derivatives of the general formula (I) wherein R1, R2, R3 and R4 are as defined in the specification below. The present invention further relates to a process for preparing the compound of formula (II) and novel crystalline structures of the compound of formula (II).

Abstract: The present invention relates to a series of peptidyl heterocyclic ketones which are inflammatory cell serine protease inhibitors and their compositions and methods for the prevention and treatment of a variety of immunomediated inflammatory disorders. More particularly, these compounds are potent and selective inhibitors of tryptase and are therefore effective for the prevention and treatment of inflammatory diseases associated with the respiratory tract, such as asthma and allergic rhinitis.

Abstract: A novel human nucleic acid and polypeptide, termed PRSS11-L, are disclosed. PRSS11-L, which is observed in tissues throughout the body, can be used in methods of detection, gene therapy, and screening.

Abstract: The invention is directed to a pharmaceutical composition of topiramate, an anticonvulsant which is useful for treating epilepsy. More specifically, the present invention provides a solid dosage formulation of topiramate intended primarily for use by pediatric patients, or for patients who have difficulty swallowing tablets. Processes for preparing the pharmaceutical composition are also described.

Abstract: A new method to capture, purify and expand antigen-specific T lymphocytes has been developed using magnetic beads coated with recombinant MHC class I molecules. This method was optimized using homogenous populations of naive T cells purified from mice transgenic for the 2C T cell receptor (TCR). These T cells were captured on beads coated with MHC class I molecules and the relevant antigenic peptides. MHC and peptide specificity was confirmed by the usage of irrelevant MHC peptide combinations. An enrichment of 800 to 1600 fold was measured, using 2C T cells mixed with irrelevant T cells, starting from a 2C T cell frequency of 1/3000. The same approach was used to purify antigen-specific CD8+ T cells from total CD8+ T cells from naive mice. The recovered cells could be expanded and specifically kill target cells in vitro; they had a significant effect in vivo as well. We expect this procedure to be suitable to purify and expand in vitro tumor- and virus-specific killer T cells for use in cell therapy.

Abstract: T-cell responses are initiated via contact with MHC/peptide complexes on antigen presenting cells (APCs). The fate of these complexes, however, is unknown. Here, using live APCs expressing MHC class I molecules fused with green-fluorescent protein, we show that peptide-specific T-cell/APC interaction induces clusters of MHC I molecules to congregate within minutes at the contact site; thereafter, these MHC I clusters are acquired by T-cells in small aggregates.,We further demonstrate that acquisition of MHC I by T-cells correlates with TCR down regulation and the APC-derived MHC I molecules are endocytosed and degraded by-T-cells. These data suggest a novel mechanism by which TCR recognition of MHC/peptide complexes can be curtailed by internalization of MHC molecules by T-cells.

Abstract: DNAs encoding the mammalian histamine H4 receptors have been cloned and characterized. These recombinant molecules are capable of expressing biologically active histamine H4 receptor protein. The cDNA's have been expressed in recombinant host cells that produce active recombinant protein. The pharmacology of known histamine ligands is demonstrated. The recombinant protein may be purified from the recombinant host cells. In addition, recombinant host cells are utilized to establish methods to identify modulators of the receptor activity, and receptor modulators are identified.

Abstract: The present invention is directed to novel 1,4-diazepines, pharmaceutical compositions thereof, and the use thereof as inhibitors of HDM2-p53 interactions.

Abstract: The present invention relates to novel substituted diamine derivatives for the formula wherein R1, R2, R3, R4, X1, X2, X3, X4, A, Y and n are as described in the specification, pharmaceutical compositions containing them and intermediates used in their manufacture. More particularly, the compounds of the invention are motilin receptor antagonists useful for the treatment of associated conditions and disorders such as gastrointestinal reflux disorders, eating disorders leading to obesity and irritable bowel syndrome.

Abstract: This invention relates resiniferatoxin derivatives useful in a vanilloid receptor binding assay and methods for production thereof.

Abstract: Aminoguanidine and alkoxyguanidine compounds are described, including compounds of the Formula VII: wherein X is O or NR9 and Het, R1, R7, R8, R12-R15, Ra, Rb, Rc, Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier.

Abstract: Anticonvulsant derivatives useful for preventing the development of Type II diabetes mellitus and Syndrome X are disclosed.